The coefficient of cyclic variation: a novel statistic to measure the magnitude of cyclic variation.

BACKGROUND: PERIODIC OR CYCLIC DATA OF KNOWN PERIODICITY ARE FREQUENTLY ENCOUNTERED IN EPIDEMIOLOGICAL AND BIOMEDICAL RESEARCH: for instance, seasonality provides a useful experiment of nature while diurnal rhythms play an important role in endocrine secretion. There is, however, little consensus on how to analysis these data and less still on how to measure association or effect size for the often complex patterns seen. RESULTS: A simple statistic, readily derived from Fourier regression models, provides a readily-understood measure cyclic variation in a wide variety of situations. CONCLUSION: The coefficient of cyclic variation or similar statistics derived from the variance of a Fourier series could provide a universal means of summarising the magnitude of periodic variation.

A randomized trial to investigate the effects of pre-natal and infant nutritional supplementation on infant immune development in rural Gambia: the ENID trial: Early Nutrition and Immune Development.

BACKGROUND: Recent observational research indicates that immune development may be programmed by nutritional exposures early in life. Such findings require replication from trials specifically designed to assess the impact of nutritional intervention during pregnancy on infant immune development. The current trial seeks to establish: (a) which combination of protein-energy (PE) and multiple-micronutrient (MMN) supplements would be most effective; and (b) the most critical periods for intervention in pregnancy and infancy, for optimal immune development in infancy. METHODS/DESIGN: The ENID Trial is a 2 x 2 x 2 factorial randomized, partially blind trial to assess whether nutritional supplementation to pregnant women (from < 20 weeks gestation to term) and their infants (from 6 to 12 months of age) can enhance infant immune development. Eligible pregnant women from the West Kiang region of The Gambia (pregnancy dated by ultrasound examination) are randomized on entry to 4 intervention groups (Iron-folate (FeFol = standard care), multiple micronutrients (MMN), protein-energy (PE), PE + MMN). Women are visited at home weekly for supplement administration and morbidity assessment and seen at MRC Keneba at 20 and 30 weeks gestation for a detailed antenatal examination, including ultrasound. At delivery, cord blood and placental samples are collected, with detailed infant anthropometry collected within 72 hours. Infants are visited weekly thereafter for a morbidity questionnaire. From 6 to 12 months of age, infants are further randomized to a lipid-based nutritional supplement, with or without additional MMN. The primary outcome measures of this study are thymic development during infancy, and antibody response to vaccination. Measures of cellular markers of immunity will be made in a selected sub-cohort. Subsidiary studies to the main trial will additionally assess the impact of supplementation on infant growth and development to 24 months of age. DISCUSSION: The proposed trial is designed to test whether nutritional repletion can enhance early immune development and, if so, to help determine the most efficacious form of nutritional support. Where there is evidence of benefit from a specific intervention/combination of interventions, future research should focus on refining the supplements to achieve the optimal, most cost-effective balance of interventions for improved health outcomes.

The dynamics of nasopharyngeal streptococcus pneumoniae carriage among rural Gambian mother-infant pairs.

BACKGROUND: Streptococcus pneumoniae is an important cause of community acquired pneumonia, sepsis, meningitis and otitis media globally and has been incriminated as a major cause of serious childhood bacterial infections in The Gambia. Better understanding of the dynamics of transmission and carriage will inform control strategies. METHODS: This study was conducted among 196 mother-infant pairs recruited at birth from six villages in the West Kiang region of The Gambia. Nasopharyngeal swabs were collected from mother-infant pairs at birth (within 12 hours of delivery), 2, 5 and 12 months. Standard techniques of culture were used to identify carriage and serotype S. pneumoniae. RESULTS: Of 46 serotypes identified, the 6 most common, 6A, 6B, 14, 15, 19F and 23F, accounted for 67.3% of the isolates from infants. Carriage of any serotype among infants rose from 1.5% at birth to plateau at approximately 80% by 2 m (prevalence at 2 m = 77%; 5 m = 86%; 12 m = 78%). Likewise, maternal carriage almost doubled in the first 2 months post-partum and remained elevated for the next 10 m (prevalence at birth = 13%; 2 m = 24%; 5 m = 22%; 12 m = 21%). Carriage was significantly seasonal in both infants and mothers with a peak in December and lowest transmission in August. The total number of different serotypes we isolated from each infant varied and less than would be expected had the serotypes assorted independently. In contrast, this variability was much as expected among mothers. The half-life of a serotype colony was estimated to be 1.90 m (CI95%: 1.66-2.21) in infants and 0.75 m (CI95%: 0.55-1.19) in mothers. While the odds for a serotype to be isolated from an infant increased by 9-fold if it had also been isolated from the mother, the population attributable fraction (PAF) of pneumococcal carriage in infants due to maternal carriage was only 9.5%. Some marked differences in dynamics were observed between vaccine and non-vaccine serotypes. CONCLUSIONS: Colonisation of the nasopharynx in Gambian infants by S. pneumoniae is rapid and highly dynamic. Immunity or inter-serotype competition may play a role in the dynamics. Reducing mother-infant transmission would have a minimal effect on infant carriage.

Maternal protein-energy supplementation does not affect adolescent blood pressure in The Gambia.

BACKGROUND: Birthweight, and by inference maternal nutrition during pregnancy, is thought to be an important determinant of offspring blood pressure but the evidence base for this in humans is lacking data from randomized controlled trials. METHODS: The offspring from a maternal prenatal protein-energy supplementation trial were enrolled into a follow-up study of chronic disease risk factors including blood pressure. Subjects were 11-17 years of age and blood pressure was measured in triplicate using an automated monitor (Omron 705IT). One-thousand two-hundred sixty seven individuals (71% of potential participants) were included in the analysis. RESULTS: There was no difference in blood pressure between those whose mothers had consumed protein-energy biscuits during pregnancy and those whose mothers had consumed the same supplement post-partum. For systolic blood pressure the intention-to-treat regression coefficient was 0.46 (95% CI: -1.12, 2.04). Mean systolic blood pressure for control children was 110.2 (SD +/- 9.3) mmHg and for intervention children was 110.8 (SD +/- 8.8) mmHg. Mean diastolic blood pressure for control children was 64.7 (SD +/- 7.7) mmHg and for intervention children was 64.6 (SD +/- 7.6) mmHg. CONCLUSIONS: We have found no association between maternal prenatal protein-energy supplementation and offspring blood pressure in adolescence amongst rural Gambians. We found some evidence to suggest that offspring body composition may interact with the effect of maternal supplementation on blood pressure.

Use of stable-isotope techniques to validate infant feeding practices reported by Bangladeshi women receiving breastfeeding counseling.

BACKGROUND: The World Health Organization recommends exclusive breastfeeding until age 6 mo. Studies relying on mothers' self-reported behaviors have shown that lactation counseling increases both the rate and duration of exclusive breastfeeding. OBJECTIVE: We aimed to validate reported infant feeding practices in rural Bangladesh; intakes of breast milk and nonbreast-milk water were measured by the dose-given-to-the mother deuterium dilution technique. DESIGN: Subjects were drawn from the large-scale Maternal and Infant Nutrition Interventions, Matlab, study of combined interventions to improve maternal and infant health, in which women were randomly assigned to receive either exclusive breastfeeding counseling or standard health care messages. Data on infant feeding practices were collected by questionnaire at monthly visits. Intakes of breast milk and nonbreast-milk water were measured in a subsample of 98 mother-infant pairs (mean infant age: 14.3 wk) and compared with questionnaire data reporting feeding practices. RESULTS: Seventy-five of the 98 subjects reported exclusive breastfeeding. Mean (+/-SD) breast milk intake was 884 +/- 163 mL/d in that group and 791 +/- 180 mL/d in the group reported as nonexclusively breastfed (P = 0.0267). Intakes of nonbreast-milk water were 40 +/- 80.6 and 166 +/- 214 mL/d (P < 0.0001), respectively. Objective cross-validation using deuterium dilution data showed good accuracy in reporting of feeding practices, although apparent misreporting was widely present in both groups. CONCLUSIONS: The dose-given-to-the-mother deuterium dilution technique can be applied to validate reported feeding behaviors. Whereas this technique shows that the reports of feeding practices were accurate at the group level, it is not adequate to distinguish between feeding practices in individual infants.